Multinational phase 2b trial of zanidatamab for HER2-amplified unresectable advanced biliary tract cancer

HER2 is overexpressed or amplified in a subset of biliary tract cancers (BTC). Zanidatamab, is a bispecific antibody targeting two distinct HER2 epitopes. The multinational phase 2b HERIZON-BTC-01 trial evaluated zanidatamab for HER2-amplified unresectable, locally advanced or metastatic BTC after progression on gemcitabine-based therapy. There were no grade 4 or 5 treatment related adverse events. Among the patients with HER2 IHC 2+ or 3+ tumors the confirmed objective response rate by independent central review was 41.3% (95% CI 30.4-52.8). The authors conclude that zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive BTC.